There is growing evidence that donor factors (age, race-ethnicity, and/or sex), method of whole blood processing, and/or the additive solution used for red cell storage could affect the quality of the red cell product and contribute to patient adverse events. For example, red cell rigidity and oxygen saturation varies between premenopausal women and postmenopausal women and men, suggesting that donor age and/or sex may be important factors affecting red cell quality and patient outcomes. A retrospective Canadian study suggested that older blood was associated with in-hospital mortality until 2006; however, after that time the risk of in-hospital mortality increased when fresher blood was transfused. This change coincided with introduction of the buffy coat method suggesting that whole blood processing methods may affect patient outcomes.

Feasibility and challenges of addressing this CQ or CC:

The most efficient way to explore these issues is through the use of large dataset that can link donor demographics, product processing and recipient transfusion and outcome data. Recipient datasets are available and the feasibility of linking blood donor and blood product information has been demonstrated, making it possible to address the research question stated above.

Name of idea submitter and other team members who worked on this idea:
Dana Devine PhD and Anne Eder MD PhD for the 2015 NHLBI State of the Science in Transfusion Medicine

Blood donation removes iron, and frequent blood donors commonly have low or absent iron stores. Donation frequency remains the strongest predictor of iron depletion among all donors, after controlling for body mass, race/ethnicity, and polymorphisms affecting iron metabolism. Less well documented is the effect of iron depletion on blood donor health and well-being. Iron deficiency may have a broad spectrum of physical and neurologic consequences, including impaired work capacity, altered cognitive function, pica and restless legs syndrome. The prevalence, duration, and severity of these conditions in blood donor populations are poorly elucidated. In contrast, modest iron deficits may be protective against cancer and cardiovascular disease. Some investigators have demonstrated the feasibility to connect donor information with clinical databases to study whether donation behavior and iron status have long-term consequences for donor health.

Feasibility and challenges of addressing this CQ or CC:

Studying the short-term clinical impact of donation-induced iron deficiency presents logistical and methodological challenges. Many outcomes of interest are not observable by blood center staff under routine procedures; further, such studies are subject to selection bias due to donor failure to return to donate following low hemoglobin deferral or adverse outcomes they associate with donation. However, given the size and demographic diversity of donor populations, even uncommon outcomes can be successfully studied under a multi-center approach. A prospective approach that doesn’t condition enrollment or completion of the study on return to donate, may avoid the methodological pitfalls. A wide array of clinical or neurological outcomes can feasibly be studied with sufficient blood centers and/or donor follow-up.

Name of idea submitter and other team members who worked on this idea:
Dana Devine PhD and Anne Eder MD PhD for the 2015 NHLBI State of the Science in Transfusion Medicine

A whole blood donation rapidly removes approximately 10% of total blood volume within about 15 minutes, providing a unique opportunity to examine how biochemical pathways regulating iron metabolism and hemoglobin biosynthesis respond to acute hemorrhage in otherwise healthy individuals. Genetic studies could examine the impact of polymorphisms of iron regulatory and hemoglobin biosynthesis proteins on the physiological responses to blood donation and recovery from blood donation or to identify previously unrecognized polymorphisms and proteins that affect dietary iron absorption and hemoglobin synthesis. Blood donor diversity might enable research into the genetic determinants of the racial variability in hemoglobin set point or the changes in biochemical responses with aging. The results of basic studies in healthy individuals may also help to understand disease mechanisms and treatments for anemia, inflammation, iron overload, bone marrow expansion/bone health, infectious diseases, neurological disorders and cancer.

Feasibility and challenges of addressing this CQ or CC:

Blood donors are often willing to participate in research studies, especially when study design allows completion in one donor visit. More complex studies requiring donor follow-up or an intervention can also be rapidly enrolled and completed based on past experience. Clinical assays to measure iron regulatory proteins are currently available and tools for complex genetic analyses are rapidly advancing. Thus, the likelihood of completing study enrollment and answering specific questions about responses of iron metabolism proteins to blood donation in a time period of 3-10 years is high.

Name of idea submitter and other team members who worked on this idea:
Dana Devine PhD and Anne Eder MD PhD for the 2015 NHLBI State of the Science in Transfusion Medicine

Blood donation is generally safe and well tolerated by most individuals, but some people will experience syncopal reactions after donating blood, such as dizziness, lightheadedness, or loss of consciousness. Injuries which occur as a result of loss of consciousness after blood donation can rarely cause significant morbidity or disability. Although uncommon, such donation-related injuries are likely underreported because they often occur after the donor leaves the blood center. Published studies on interventions that reduce the risk of reactions have not shown an effect on preventing injuries, although some incidents might still be preventable. Physiologists have successfully treated syncope in patients with dysautonomia, in trained athletes, in astronauts, in pilots and others, using physical maneuvers with muscle tensing, to almost instantly increase venous return, cardiac output and cerebral perfusion. But studies on the use of physical maneuvers during blood donation have yielded conflicting results. Further efforts are needed to design, implement and monitor strategies to reduce injuries after blood donation and optimize donor health.

Feasibility and challenges of addressing this CQ or CC:

Injuries are most commonly associated with syncopal reactions which occur after the blood donor leaves the collection site and resumes normal daily activities. Reducing injuries will require identifying susceptible donors, providing them with postdonation instructions, and improving their ability to recognize prodromal symptoms and respond to orthostatic changes in blood pressure. Technology for personalized medicine platforms, such as mobile phone apps, could be developed to capture information about post-donation reactions and facilitate real-time interactions with blood donors. Such a system would also enable blood centers to design and deliver intervention and continuously monitor the effectiveness of the approach to prevent postdonation injuries.

Name of idea submitter and other team members who worked on this idea:
Anne Eder MD PhD and Dana Devine PhD for the 2015 NHLBI State of the Science in Transfusion Medicine

Voting

Is there a risk-based framework for evaluating the blood donor selection process, to capture relevant risk factors for transfusion-transmitted diseases, while modifying policies that do not contribute to transfusion safety?

Precautionary measures have been essential to blood safety, but the precautionary principle requires periodic evaluation of donor selection policies as information emerges on their risk, benefit, and cost. For example, the HHS Advisory Committee on Blood and Tissue Safety and Availability recently called for efforts to evaluate the effectiveness of blood donor educational materials and screening questions. Recent research provided a cognitive evaluation of the Donor History questionnaire, assessment of contemporary risk factors for transfusion-transmitted infections, and insight into non-compliance with the current MSM donor deferral policy. Consequently, FDA announced in December 2014 their intent to recommend a change the deferral period for men who have had sex with men (MSM) from an indefinite period to one year. A framework is needed to evaluate other deferral policies to identify relevant risk factors among prospective donors, and modify those questions that do not contribute to blood safety. In addition, the factors that influence blood donors’ compliance and comprehension of the educational material and questions are incompletely characterized but strongly influence the effectiveness of the screening process and validity of the information elicited by the questionnaire. Rational and prudent donor selection, deferral and retrieval policies are crucial to protect transfusion recipients while encouraging repeat blood donation among healthy, motivated individuals.

Feasibility and challenges of addressing this CQ or CC:

Blood centers collect and manage large volumes of information on blood donors, donations, and components after distribution and have successfully collaborated on pilot and exploratory studies to define, collect and analyze specific data to probe specific research questions about donor eligibility criteria. Continued collaboration among blood collection sites should allow for broad representation of blood donors in future research studies which will increase their generalizability.

Name of idea submitter and other team members who worked on this idea:
Anne Eder MD PhD and Dana Devine PhD for the 2015 NHLBI Stateof the Science in Transfusion Medicine

To extend our knowledge of the pathobiology of heart, lung, blood, and sleep disorders and enable clinical investigations that advance the prediction, prevention, preemption, treatment, and cures of human disease.